Project Summary For many environmental exposures the most sensitive period of risk for later child health is pregnancy and the perinatal period, and these exposures are best ascertained from maternal self-report, biological specimens and objective environmental data collected during pregnancy and immediately after birth. This study will examine this sensitive period, measuring environmental contaminants, nutritional factors and inflammation in some 2,000 mother infant pairs in the context of their social and psychological environment. We have two cohorts totaling nearly 1,000 women enrolled, interviewed and sampled early in pregnancy (most before 14 weeks) with biological specimens archived, and are now expanding the larger of our two cohorts to a statewide probability sample of Michigan hospitals and clinics to enroll 1,000 more pregnancies. We are in contact with more than 84% of our extant cohort members. We will use newborn dried blood spots (NDBS) from the Michigan Neonatal Biobank to further quantify environmental exposures, examine epigenomic changes, and, by accessing both the child's and the mother's newborn spots, study environmental effects across generations. In Flint, MI we will examine the effects of recent water contamination on fetus and child. We will focus on three important exposures in pregnancy. First, we will determine the effects of persistent organic pollutants (POPs) and heavy metals on cognitive outcomes. We hypothesize that the effects of these toxins will be mediated by epigenetic changes measured on NDBS, and will be amplified by grant-maternal exposure (measured on mother's blood spot when she was a newborn). We hypothesize that recent in utero lead exposure in Flint, MI, as assessed in NDBS, and in the shed teeth of exposed children, will also be associated with impaired cognitive outcomes. Second, we will assess the effect of maternal nutritional and weight status in pregnancy on cognitive outcomes and childhood obesity, with a special focus on low pregnancy iodine and/or iron status, agents interfering with thyroid iodine uptake (perchlorate, thiocyanate), abnormal thyroid hormone function and pregnancy-related weight changes. Finally, we will assess the effects of pregnancy viral infection and maternal obesity on perinatal outcomes and behavior related to the autism spectrum. The effects of viral infections and maternal obesity are hypothesized to be mediated by increased placental and neonatal inflammation. The infant gut microbiome will also be assessed, as we anticipate that it may be a pathway linking both nutritional factors and pregnancy inflammation to adverse child health outcomes.